The purpose of the proposed project is to explore the relationship between the clinical course and outcome of senile dementia of the Alzheimer type (SDAT) and impaired cholinergic and noradrenergic innervation of cerebral cortex. Patients referred for evaluation of dementia will be seen by a neurologist, (HCC), psychiatrist, and clinical psychologist. There will be a complete workup including: blood chemistries, electroencephalogram computed tomogram of the head, and formal psychological assessment. The clinical and neurological findings will be correlated with the post-mortem brain evaluation. A histopathological study will determine the type of dementia. Specimens of the substantia innominata (origin of some of the cholinergic axons terminating in the cerebral cortes), the locus ceruleus (origin of nearly all the noradrenergic axons projecting to the cerebral cortex), and the substantia nigra (origin of the dopaminergic innervation of the neostriatum) will be assessed. These specimens will be studiesd for the presence of cells containing catecholamines, acetycholinesterase, dopamine beta-Hydroxylase, cytoplasmic RNA, and lipofucsin using histological, histochemical and immunohistochemical techniques. Control brains from elderly patients without a history of dementia or with dementia due to causes other than SDAT will be similarly studied. This project will test the proposition that SDAT, in contrast to other dementias, involves abnormalities in at least two transmitter-specific nuclei of the forebrain and brainstem. Improved characterization of changes in these two neuronal populations in relation to clinical signs and symptoms will hopefully contribute to a better understanding and possible pharmacological treatment for Alzheimer's Disease.